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Báo cáo khoa học: "The synchronous occurrence of squamous cell carcinoma and gastrointestinal stromal tumor (GIST) at esophageal site"

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Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: The synchronous occurrence of squamous cell carcinoma and gastrointestinal stromal tumor (GIST) at esophageal site

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World Journal of Surgical Oncology BioMed Central Open Access Case report The synchronous occurrence of squamous cell carcinoma and gastrointestinal stromal tumor (GIST) at esophageal site Gian Paolo Spinelli1,2, Evelina Miele1, Federica Tomao3, Luigi Rossi2, Giulia Pasciuti2, Angelo Zullo4, Federica Zoratto2, Jose Nunnari5, Giovanni Codacci Pisanelli1,2 and Silverio Tomao*1,2 Address: 1Department of Experimental Medicine, University of Rome "Sapienza", Rome, Italy, 2Universitary Oncology, S.M Goretti Hospital, Latina, Italy, 3Department of Gynaecology Perinatology and Puericulture Science, University of Rome "Sapienza", Rome, Italy, 4Gastroenterology and Digestive Endoscopy, "Nuovo Regina Margherita" Hospital, Rome, Italy and 5Pathologic Anatomy, San Camillo-Forlanini Hospital, Rome, Italy Email: Gian Paolo Spinelli - gianpaolo.spinelli@uniroma1.it; Evelina Miele - evelina.miele@uniroma1.it; Federica Tomao - tomao.smfa@tiscali.it; Luigi Rossi - gigireds.s@libero.it; Giulia Pasciuti - giulia.pasciuti@libero.it; Angelo Zullo - giaggio.s@libero.it; Federica Zoratto - federica.z@libero.it; Jose Nunnari - tremotti@sancamilloforlanini.rm.it; Giovanni Codacci Pisanelli - giovanni.codacci@uniroma1.it; Silverio Tomao* - silverio.tomao@uniroma1.it * Corresponding author Published: 5 November 2008 Received: 20 February 2008 Accepted: 5 November 2008 World Journal of Surgical Oncology 2008, 6:116 doi:10.1186/1477-7819-6-116 This article is available from: http://www.wjso.com/content/6/1/116 © 2008 Spinelli et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Esophageal squamous cell carcinoma is a relative common malignancy with a very poor prognosis, even adopting an integrated and multidisciplinary approach. According to the literature, gastrointestinal stromal tumors (GISTs) rarely originate from the esophagus. Moreover there are not reports of synchronous occurrence of squamous cell carcinoma and GIST at esophageal site. Case presentation: We describe a case of a 74 year old patient who underwent surgery for squamous cell carcinoma of the lower third of the esophagus with an incidental pathologic diagnosis of a concomitant GIST in the thoracic tract. Conclusion: In literature there is no evidence of concomitant squamous carcinoma and GIST of the thoracic esophagus, even if esophageal GISTs are sometimes described. The occasional finding of this neoplastic lesion underlines the importance of a carefully pathological diagnosis for its identification. Surgery, followed by a multidisciplinary approach remains the first-line treatment in both squamous and stromal neoplasm. tro-esophageal junction; therefore a GIST located at the Background GISTs are the most frequent non epithelial neoplasms of level of the thoracic esophagus is extremely rare. Many the gastrointestinal tract, with a preferred gastric localiza- esophageal GISTs are diagnosed after the onset of clinical tion (about 60% in the stomach and 20–30% in the intes- symptoms, or sometimes discovered by chance, during tine). The esophageal location is very uncommon and routine examinations (diagnostic endoscopy procedures, represents approximately 5% of gastrointestinal GISTs. In transesophageal echocardiograms or surgical procedures addition, the majority of esophageal GISTs arise at the gas- carried out for other reasons). The diagnosed incidentally Page 1 of 5 (page number not for citation purposes)
World Journal of Surgical Oncology 2008, 6:116 http://www.wjso.com/content/6/1/116 GISTs tend to be smaller in terms of centimetres and they with a maximum diameter of 0.2 cm, and with morpho- already present the mutation at the KIT level. The elective logical characteristics suggesting a very low risk GIST (Fig- treatment for these tumors is esophagectomy, paying par- ure 2A, B). ticular attention to excision of the mucosa, sub mucosa and the muscular areas and of the surrounding per- The immunohistochemistry of the fused cells showed an iesophageal tissues. intense and diffuse positivity for CD117, CD34 and CD99 and negative results for S100, desmin and actin (Figure 3A, B). The proliferate index Ki 67 was less than 5% with Case presentation We describe a case of a 74 year old male patient, affected 4 mitoses per 50 HPF. by a myeloproliferative syndrome. At the age of 26 he underwent a surgical gastrectomy for a hemorrhage The aspects of this lesion reminded palisading-vacuolated caused by a perforated ulcer. Later, in December 2006, an spindle cell GISTs. In fact it showed nuclear palisading, upper gastrointestinal endoscopy revealed a neoplasm at resembling peripheral schwannomas and the typical fea- the level of the thoracic esophagus. Multiple tissue biop- ture of prominent perinuclear vacuolization. sies histologically showed a scarcely differentiated squa- mous cell carcinoma. Subsequently all the necessary In May 2007, a total body CT scan showed the presence of staging exams, including a total body Computed Tomog- necrotic-hemorrhagic foci, of probable ischemic nature, raphy (CT) were performed. The CT did not show any sus- in the cortical and sub cortical brain regions. At the same pected lymph nodes nor other lesions. In March 2007 the time, the thoracic region showed the presence of diffuse patient underwent a total esophagectomy and an micro nodules in the lungs, associated with chronic bron- esophago-gastroplasty with colon interposition for chial and peribronchial wall thickening. We also noticed replacement of the esophagus. a modest splenomegaly (22 cm) and, at the aortic-pulmo- nary window, in the inferior pre-tracheal and right hilum areas, several lymph nodes of 13 mm. Considering the Histological examination The final histological findings confirmed the diagnosis of pathological and clinical staging, the patient did not infiltrating squamous cell carcinoma; (Figure 1,A, B). The require chemotherapy treatment, and would continue his lesion extended into the sub mucosal layer, a grade G3 follow-up with routine examinations. was diagnosed and the surgical margins were considered free of infiltration. Since the regional lymph nodes were Discussion not reported, the final staging was pT1 pNx. In addition, a The term Gastric Stromal Tumors was first coined in 1983 sample was taken at a distance from the original tumor as by Mazur and Clark [1], to describe a heterogeneous an occasional finding in the esophageal muscular tunica. group of mesenchimal tumors that did not exhibit classic This showed a fused cellular intramural micro nodule features of muscular differentiation. However only in A B Figure 1 Microscopic examination of squamous cell carcinoma Microscopic examination of squamous cell carcinoma. A) Esophagus infiltrative squamous cell carcinoma (H and E 10×); B) Esophagus infiltrative squamous cell carcinoma (H & E 20×); Page 2 of 5 (page number not for citation purposes)
World Journal of Surgical Oncology 2008, 6:116 http://www.wjso.com/content/6/1/116 A B Figure 2 Microscopic examination of GIST Microscopic examination of GIST. A) Intramural nodule of gastrointestinal stromal tumour (GIST) (H & E 10×); B) Fascic- ular arrangement of spindle cells with prominent nuclear palisade in GIST (H & E 10×); 1998 Kindblom et al [2], revealed the expression of the The median age of onset is 60–69 years and the symptoms antigen CD 117 and Hirota et al. [3], first identified a gain are usually non-specific such as tiredness, abdominal dis- of function mutations at the level of the proto-oncogene comfort and gastro-intestinal bleeding. The main instru- c-KIT (CD 117) in this neoplasm, which is regarded to be ments used for the diagnosis of GISTs are CT scans and pivotal in the development of most GISTs. These very sug- PET scans. gestive neoplasias are extremely rare and tend to be local- 18F-FDG PET seems to have lower sensitivity than CT for ized at the gastric level (60–70%) and small intestine (20– 30%); with smaller percentages these lesions have been gastrointestinal stromal tumors staging. However PET is described in other regions such as the large intestine, rec- superior in monitoring therapeutic treatment response to tum, and omentum and with an incidence of less than 5% imatinib in patients with malignant GISTs. CT and PET in the esophagus [4]. are complementary and PET/CT techniques have been A B Figure – Immuno3 staining of GIST Immuno – staining of GIST. A) KIT (CD117) immuno-staining in GIST. The tumor cells show strong cytoplasmic and peri- nuclear positivity; B) Negative immuno-staining for Desmin in GIST. Page 3 of 5 (page number not for citation purposes)
World Journal of Surgical Oncology 2008, 6:116 http://www.wjso.com/content/6/1/116 shown to be useful in diagnosis, staging and treatment According to our epidemiological knowledge the hypoth- response in GISTs [5-7]. Based on parameters such as size esis of a common etiopathogenesis at esophageal site, for and number of mitosis, these neoplasias can be subdi- GIST and esophageal squamous cell carcinoma cannot be vided into different risk classes: high, intermediate, low supported. However we could hypothesize that develop- and very low. ment of these tumors may involve common carcinogen antigens, making the synchronous occurrence of GIST and Positivity for the CD117 is the key feature of GIST, but other abdominal malignancy not only a coincidence. CD34 and nestin are other commonly expressed but less GIST-specific antigens. Moreover, these tumors can be Conclusion positive for smooth muscle markers and generally nega- Our case report seems to be the only one described in a tive for desmine. S-100 protein expression is rare and glial patient with a myeloproliferative syndrome, esophageal fibrillary acidic protein is not present. Keratine 18 and squamous cell carcinoma and GIST. The occasional find- Keratine 8 are occasionally expressed. ing of this latter neoplastic lesion underlines once more the importance of a carefully pathological diagnosis and a CD99 is not required for GIST diagnosis, but as its immu- multidisciplinary approach. Of course, surgery [19,20] noreactivity is not uncommon in a variety of soft tissue remains the first-line treatment in both squamous and tumors, correlation of expression of this marker with that stromal neoplasms. of other immunomarkers and with morphology is war- ranted [8]. Consent Written consent was obtained from the patient for publi- Gastrointestinal (true) smooth muscle tumors, nerve cation of this case report. sheath tumors, desmoids, inflammatory myofibroblastic tumors, inflammatory fibroid polyps, and undifferenti- Competing interests ated sarcomas are the most commonly confused with The authors declare that they have no competing interests. GISTs. Rarely, poorly-differentiated carcinomas and histi- ocytic sarcoma can also take a part into differential diag- Authors' contributions nosis which is usually importantly aided by GPS conceived of the study, partecipated in its design and immonohistochemistry. These tumors have been reported drafting. EM conceived of the study, partecipated in its as c-KIT negative but with other peculiar markers, gener- design and drafting. FT participated in the design of the ally not expressed in GISTs [9]. study and collect the clinical data. LR participated in the design of the study and collect the clinical data. GP partic- The differential diagnosis among GISTs and other epithe- ipated in the design of the study and collect the clinical lial neoplastic lesions of the gastro-intestinal tract is very data. AZ participated in the design of the study and collect important. In fact 95% of these tumors express the trans- the clinical data. FZ participated in the design of the study membrane receptor with tyrosine kinase activity c-kit, and and collect the clinical data. GCP participated in the above all this group of lesions tends to show an interest- design of the study and collect the clinical data. JN carried ing response (sometimes dramatic) to new target treat- out the histopathological evaluation. ST conceived of the ments [3,10-12]. study, participated in its design and coordination and helped to draft the manuscript. All authors read and Clinical studies have shown that the elective medical approved the final manuscript. treatment for patients with inoperable lesions is imatinib (400 mg/die) with positive responses above 50% [13]. References The use of other treatments such as Sunitinib, another 1. Mazur MT, Clark HB: Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 1983, 7(6):507-519. tyrosine kinase inhibitor, has been approved in patients 2. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM: Gas- who do not respond to treatment with imatinib, and gen- trointestinal pacemaker cell tumour (GIPACT): gastrointes- tinal Stromal tumors show phenotypic characteristics of the erally present a mutation of the exon 9 of c-kit [13,14]. interstitial cells of Cajal. Am J Pathol 1998, 152(5):1259-1269. 3. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Esophageal GISTs are rarely described in literature, and no Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y: Gain-of-func- cases of both GIST and squamous cell carcinoma have tion mutations of c-kit in human gastrointestinal stromal been reported. On the contrary, other kind of tumors have tumors. Science 1998, 279:577-80. 4. Corless CL, Fletcher JA, Heinrich MC: Biology of gastrointestinal been found together (synchronous or metachronous) stromal tumors. J Clin Oncol 2004, 22(18):3813-3825. with GISTs in the gastrointestinal system, such as low 5. Gayed I, Vu T, Iyer R, Johnson M, Macapinlac M, Swanston N, Podoloff grade malign lymphoma and GIST in stomach, colorectal D: The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal cancer, gastric cancer, small bowel or mesenterium tumors. J Nucl Med 2004, 45(1):17-21. tumors and carcinoid of pancreas [15-18]. Page 4 of 5 (page number not for citation purposes)
World Journal of Surgical Oncology 2008, 6:116 http://www.wjso.com/content/6/1/116 6. Alberini JL, Al Nakib M, Wartski M, Gontier E, Cvitkovic F, Rixe O, Rougier P, Pecking AP: The role of PET scan in gastrointestinal stromal tumors. Gastroenterol Clin Biol 2007, 31(6–7):585-93. 7. Goldstein D, Tan BS, Rossleigh M, Haindl W, Walker B, Dixon J: Gas- trointestinal stromal tumors: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response – an AGITG study. Oncology 2005, 69(4):326-32. 8. Shidham VB, Chivujula M, Gupta D, Rao RN, Komorowski R: Immu- nohistochemical comparison of gastrointestinal stromal tumor and solitary fibrous tumor. Arch Pathol Lab Med 2002, 126:1189-1192. 9. Miettinen M, Lasota J: Gastrointestinal stromal tumors. Review on morphology, molecular pathology, prognosis and differ- ential diagnosis. Arch Pathol Lab Med 2006, 130:1466-1478. 10. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW: Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002, 33:459-465. 11. Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA: KIT extra cellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 2000, 156:791-795. 12. Rubin BP, Fletcher JA, Fletcher CD: Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Pathol 2000, 8(1):5-10. 13. Siehl J, Thiel E: C-kit, GIST, and imatinib. Recent Results Cancer Res 2007, 176:145-151. 14. Fletcher JA, Rubin BP: KIT Mutations in GIST. Current Opinion in Genetics & Development 2007, 17(1):3-7. 15. Wronski M, Ziarkiewicz-Wroblewska B, Gornika B, Cebulski W, Slodkowskj M, Wasiutynski A, Ktasnodebski IW: Synchronous occurrence of gastrointestinal stromal tumors and other pri- mary gastrointestinal neoplasms. World J Gastroenterol 2006, 12(33):5360-5362. 16. Melis M, Choi EA, Anders R, Christiansen P, Fichera A: Synchro- nous colorectal adenocarcinoma and gastrointestinal stro- mal tumor (GIST). Int J Colorectal Dis 2007, 22:109-114. 17. Kalmár K, Tornóczky T, Pótó L, Illényi L, Kalmár Nagy K, Kassai M, Kelemen D, Horváth OP: Gastrointestinal stromal tumors in a single institute: is there an association to other gastrointes- tinal malignancies? Magy Seb 2004, 57(5):251-6. 18. Kövér E, Faluhelyi Z, Bogner B, Kalmár K, Horváth G, Tornóczky T: Dual tumors in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms. Magy Onkol 2004, 48(4):315-21. 19. Abraham SC, Krasinskas AM, Hofstetter WL, Swisher SG, Wu TT: "Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. Am J Surg Pathol 2007, 31(11):1629-35. 20. Blum MG, Bilimoria KY, Wayne JD, de Hoyos AL, Talamonti MS, Adley B: Surgical considerations for the management and resection of esophageal gastrointestinal stromal tumors. Ann Thorac Surg 2007, 84(5):1723. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 5 of 5 (page number not for citation purposes)

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